Natural cell-mediated cytotoxicity of mouse and rat lymphocytes against tumors and other target cells was studied in a short-term 51Cr release assay. Natural killing (NK) in mice was shown to be directed against a variety of mouse tumors, including lymphomas, carcinomas and sarcomas, and against some normal cells: thymus cells, bone marrow cells and macrophages. NK activity against heterologous tumor cells was also demonstrated. The majority of NK cells in mice and rats were found to have Fc receptors for IgG and to bear low densities of T cell markers. NK activity was strongly boosted 3 days after inoculation of antigenic tumor cells, lymphocytic choriomeningitis virus, BCG or C. parvum. This effector mechanism appears to play an important role in vivo resistance against tumor growth and bone marrow transplantation. The cell-mediated immune response of W/Fu rats to a syngeneic lymphoma was also studied. Upon removal of suppressor macrophages from spleens of immunized rats, lymphoproliferative responses to the tumor cells were shown to be long-lasting. Other parameters of the cell-mediated immune response (secondary generation of cytotoxicity, production of migration inhibitory factor, resistance to tumor challenge, and adoptive transfer of this resistance) were also shown to be persistent. BIBLIOGRAPHIC REFERENCES: Glaser, M. and Herberman, R.: Secondary cell-mediated cytotoxic response to challenge of rats with syngeneic Gross virus-induced lymphoma. J. Natl. Cancer Inst. 56:1211-1215, 1976. Ting, C.C., Park, J.Y., Nunn, M.E. and Herberman, R.B.: Comparison of three isotopic assays of cell-mediated cytotoxicity against mouse tumor cells. I. Basic Parameters: Baseline controls, target cells, and methods of calculation. J. Natl. Cancer Inst. 58: 323-330, 1977.